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Purpose: The aims of the study were to monitor circulating lymphocyte subset counts before and after therapy for nasopharyngeal carcinoma (NPC), and investigate their relationships with patient outcomes. Patients and Methods: Subjects comprised patients with TNM stage I–IVA NPC who underwent radiotherapy. Peripheral venous blood samples were collected before and after treatment. Lymphocyte subset counts were analyzed by flow cytometry. Differences between post-treatment and baseline counts were calculated to determine Δ values. Patients were divided into high and low groups, based on median lymphocyte subset counts; propensity score matching was applied to balance groups. Progression-free survival (PFS) and overall survival (OS) were plotted using Kaplan-Meier curves and compared using a Log rank test. Relationships between lymphocyte subset counts and patient survival were subjected to Cox regression analysis. Results: Patients with NPC (n=746) were enrolled from 2012– 2022. Higher CD8+ and total T cell baseline counts were associated with better 5-year PFS (73.7% vs 63.1%, P=0.002 and 73.8% vs 64.1%, P=0.005, respectively). Similarly, higher Δ values of CD4+ and total T cells were associated with higher 5-year PFS (76.2% vs 63.5%, P=0.001; 74.3% vs 65.4%, P=0.010) and OS (89.8% vs 81.6%, P=0.005; 88.6% vs 82.5%, P=0.009). Multivariate Cox regression revealed that CD8+ (hazard ratio (HR) 0.651, P=0.002) and total T (HR 0.600, P< 0.001) cells were significantly associated with PFS. CD4+ (HR 0.708, P=0.038) and total T (HR 0.639, P=0.031) cells were independent prognostic factors for OS. Conclusion: NPC patients with low total or CD8+ T cell counts before treatment had worse prognosis; however, those with more significant decreases in total or CD4+ T cells possibly had better outcomes. T cell counts can be reliable indicators to predict prognosis. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the efficacy of chemotherapy among intermediate-risk (stage II/T3N0) nasopharyngeal carcinoma (NPC) patients receiving radiotherapy (RT). Methods: We identified stage II/T3N0 NPC patients who received radiotherapy with or without chemotherapy from the Surveillance, Epidemiology and End Results database (2004–2019). Overall survival (OS) and cancer-specific survival (CSS) were assessed using the Kaplan–Meier method with log-rank test and Cox proportional hazards models to evaluate the efficacy of chemotherapy. Subgroup analysis was also conducted based on the baseline characteristics. Propensity score matching (PSM) was performed to balance the intergroup covariates. Results: A total of 1623 patients were enrolled in the study, 1444 received chemoradiotherapy (CRT) and 179 received RT alone. CRT, compared to RT alone, was independently associated with a better OS (HR 0.57, 95% CI 0.45–0.71) and CSS (HR 0.55, 95% CI 0.39–0.79). After PSM, similar results were obtained, and CRT was superior to RT alone in terms of OS (HR 0.60, 95% CI 0.39–0.92) and CSS (HR 0.60, 95% CI 0.40–0.91). Subgroup analysis revealed that OS benefits from CRT were mainly observed in T0-2N1(HR 0.51, 95% CI 0.38–0.70) and T3N0 (HR 0.64, 95% CI 0.42–0.98) rather than T2N0 (HR 1.00, 95% CI 0.51–1.94). Interestingly, after PSM, OS benefits were still seen in T0-2N1 (HR 0.44, 95% CI 0.24–0.82), while not seen in T2N0 (HR 1.83, 95% CI 0.56–5.97) and T3N0 (HR 0.56, 95% CI 0.28–1.12). Conclusion: For T0-2N1 NPC patients, CRT was superior to RT alone with better survival, whereas, for T2-3N0 patients, CRT was comparable to RT alone. Prospective large studies should be encouraged to verify the results. [ABSTRACT FROM AUTHOR]

Background: The optimal number of cycles of induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (LANPC) is unclear. We aimed to combine the tumor response during IC and tumor stage to individualize the number of IC cycles. Methods: Totally, 498 LANPC patients who received IC plus CCRT between 2014 and 2018 were reviewed. Tumor response during IC was used to stratify patients with different risks. All patients were classified into those who received two cycles of IC and those who were treated with three cycles. Propensity score matching methods were performed to compare the treatment efficiency. Results: After two cycles of IC, 340/498 (68.3%) cases showed complete tumor response (CR)/partial response (PR) and 158 (31.7%) achieved stable disease (SD)/disease progression (PD). Unfavorable responders (SD/PD) exhibited poor survival outcomes. The three‐cycle IC regimen was correlated with better OS and PFS than the two‐cycle regimen for N2‐3 patients in the CR/PR group. However, the use of different IC cycle strategies achieved similar survival outcomes for SD/PD or N0‐1 patients. The incidences of acute toxicities were higher in the IC = 3 group. Conclusions: Tumor response during IC could be a powerful predictor of LANPC and could be used to guide the individualized number of IC cycles. A three‐cycle IC regimen seemed to be preferable for N2‐3 patients who received CR/PR during IC. However, an additional cycle of IC could not benefit N0‐1 or SD/PD patients, and the optimal treatment strategies for these patients require further consideration. [ABSTRACT FROM AUTHOR]

Background: The prognostic significance of wait time between definite diagnosis and initial radical radiotherapy is not well established in patients with locoregionally advanced nasopharyngeal carcinoma (LA‐NPC) receiving both induction chemotherapy (IC) and concurrent chemoradiotherapy (CCRT). Methods: From 2010 to 2018, 648 patients with LA‐NPC treated with IC followed by CCRT were included. Results: A total of 172 pairs of patients with LA‐NPC were selected by propensity score matching (PSM). Compared to patients with an acceptable wait time (≤75 days), patients with a prolonged wait time (>75 days) had a significant lower 5‐year DMFS rate (86.6% vs. 74.1%, p = 0.006). Subgroup analyses indicated that the unfavorable effects of longer waiting times were mainly seen among stage IVa patients. Conclusions: A prolonged wait time (>75 days) between definite diagnosis and initial radical radiotherapy has negative prognostic effects on patients with LA‐NPC receiving IC plus CCRT, particularly those with IVa stage. [ABSTRACT FROM AUTHOR]

Background: The optimal cumulative cisplatin dose (CCD) during radiation therapy for locoregionally advanced nasopharyngeal carcinoma (LA‐NPC) patients receiving induction chemotherapy (IC) plus CCRT remains controversial. This study aimed to explore the treatment efficiency of CCD for high‐and low‐risk patients with LA‐NPC. Methods: Data from 472 LA‐NPC patients diagnosed from 2014 to 2018 and treated with IC plus CCRT were reviewed. After propensity score matching, the therapeutic effects of a CCD > 200 and CCD ≤ 200 mg/m2 were evaluated comparatively. Five factors selected by multivariate analysis were incorporated to develop a nomogram. Subgroup analysis was conducted to explore the role of different CCDs in nomogram‐defined high‐ and low‐risk groups. Additionally, acute toxicities were evaluated comparatively between the high‐ and low‐CCD groups. Results: After matching, there was no difference between different CCD groups for all patients in terms of 3‐year overall survival (OS), distant metastasis‐free survival (DMFS), locoregional recurrence‐free survival (LRRFS), or progression‐free survival (PFS). A nomogram was built by integrating pretreatment EBV DNA, clinical stage, and post‐IC EBV DNA, post‐IC primary gross tumor and lymph node volumes obtained a C‐index of 0.674. The high‐risk group determined by the nomogram had poorer 3‐year PFS, OS, DMFS, and LRRFS than the low‐risk group. A total of CCD > 200 mg/m2 increased the survival rates of 3‐year PFS and DMFS (PFS: 72.5% vs. 54.4%, p = 0.012; DMFS: 81.9% vs. 61.5%, p = 0.014) in the high‐risk group but not in the low‐risk group. Moreover, the high CCD increased treatment‐related acute toxicities. Conclusions: A high CCD was associated with better 3‐year PFS and DMFS rates than a low dose for high‐risk patients but could not produce a survival benefit for low‐risk patients. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy and safety of induction chemotherapy (IC) combined with concurrent chemoradiotherapy (CCRT) versus CCRT combined with adjuvant chemotherapy (AC) in patients with stage II–IVA nasopharyngeal carcinoma (NPC), we conducted a retrospective study and a meta-analysis combining the results of our studies. Patients and Methods: We used the propensity score matching (PSM) to balance variables. A total of 168 patients were chosen by one-to-two PSM, including 101 patients with IC + CCRT and 67 cases with CCRT + AC. We used the Kaplan–Meier curve to compare survival outcomes and also used Cox regression analysis to determine independent prognostic factors. For meta-analysis, we determined the related studies by searching the PubMed database. We used STATA v12 software to perform meta-analysis of the extracted data and calculate pooled hazard ratios, 95% confidence intervals of survival outcomes, and risk ratios for the toxicities. Results: In this retrospective study, there was no significant difference in 5-year overall survival (76.9% vs. 79.0%, P = 0.966), progression-free survival (71.3% vs. 68.5%, P = 0.332), distant metastasis-free survival (80.5% vs. 74.2%, P = 0.140), and locoregional relapse-free survival (91.5% vs. 91.8%, P = 0.894) among patients with NPC with IC + CCRT versus CCRT + AC after PSM. For meta-analysis, six articles (including our study) reporting 1,052 cases of IC + CCRT and 883 cases of CCRT + AC were included in the meta-analysis. There was no difference of OS (pooled HR = 0.90, 95% CI: 0.63–1.29, P = 0.561), PFS (pooled HR = 1.07, 95% CI: 0.87–1.33, P = 0.633), DMFS (pooled HR= 0.98, 95% CI: 0.76-1.25, P =0.861), and LRRFS (pooled HR = 1.06, 95% CI: 0.76–1.48, P = 0.724). Conclusion: The efficacy of IC + CCRT and CCRT + AC was comparable in patients with stage II–IVA NPC. In terms of compliance and acute adverse reactions, IC + CCRT may be a potential therapeutic strategy. [ABSTRACT FROM AUTHOR]

Purpose: To identify whether chemoradiotherapy improves survival in patients with stage T3‐4N0M0 nasopharyngeal carcinoma (NPC). Materials and methods: The data of patients with stage T3‐4N0M0 NPC were extracted from the Surveillance, Epidemiology, and End Results database between 2004 and 2016. The patients were divided into radiotherapy and chemoradiotherapy groups. Overall survival (OS) and cancer‐specific survival (CSS) were assessed using the Kaplan‐Meier method and propensity score matching (PSM) analyses. Results: We examined 496 patients: 88 who received radiotherapy and 408 who received chemoradiotherapy. Before PSM, chemoradiotherapy was associated with a better 5‐year OS (52.58% vs. 38.13%; P =.005) and similar CSS (63.62% vs. 59.26%; P =.196) compared to those associated with radiotherapy. However, chemoradiotherapy was not an independent prognostic factor for OS [hazard ratio (HR)=0.95, 95% confidence interval (CI): 0.68‐1.32; P =.760] or CSS (HR = 1.02, 95% CI: 0.66‐1.56; P =.935). After PSM, similar OS (45.15% vs. 42.78%; P =.626) and CSS (58.22% vs. 60.37%; P =.730) were found between the radiotherapy and chemoradiotherapy groups. Conclusion: Radiotherapy and chemoradiotherapy are associated with similar OS and CSS in patients with stage T3‐4N0M0 NPC. [ABSTRACT FROM AUTHOR]

Purposes: To evaluate retropharyngeal lymph node metastasis on N stage of nasopharyngeal carcinoma (NPC). Methods: NPC patients were extracted from the Surveillance, Epidemiology, and End Results database between 2004 and 2016. Pathologically confirmed patients with complete data of retropharyngeal lymph node metastasis were investigated. The included patients were divided into N1a and N1b groups. Overall survival (OS) and cancer-specific survival (CSS) were assessed using the Kaplan–Meier method and propensity score matching (PSM) analyses. Results: This retrospective cohort study examined 759 patients: 70 who were stage N1a and 689 who were stage N1b. Before PSM, N1a group was associated with similar 5-year OS (77.7% vs. 72.4%; P = 0.15) and CSS (85.6% vs. 79.9%; P = 0.09) compared to N1b group. After PSM, a similar OS (75.0% vs. 60.7%; P = 0.12) was found between the radiotherapy and chemoradiotherapy groups. However, N1a group showed a better 5-year CSS (83.8% vs. 71.1%; P = 0.04) compared to N1b group. Stage N1b was an independent risk prognostic factor for CSS (hazard ratio = 2.54, 95% confidence interval: 1.02–6.34; P = 0.04). Conclusions: OS was not different between N1a and N1b groups. Retropharyngeal lymph node metastasis defined as stage N1 of the 8th edition American Joint Committee on Cancer staging system is reasonable. [ABSTRACT FROM AUTHOR]

• Contradictory results have been reported for the potential survival benefit of radiation therapy for metastases. • We investigated the efficacy of metastatic lesion radiotherapy (MLRT) in patients with metastatic nasopharyngeal carcinoma (mNPC). • We found that MLRT offers substantial survival advantages to patients with mNPC. • The recommended regimen for MLRT is to employ a minimum biologically effective dose (BED) of 56 Gy to achieve optimal outcomes. We investigated the efficacy of metastatic lesion radiotherapy (MLRT) in patients with metastatic nasopharyngeal carcinoma (mNPC). Patients with mNPC from three institutions were included in this study. Propensity score matching (PSM) was employed to ensure comparability between patient groups. Overall survival (OS) rates were assessed using the Kaplan–Meier method and compared using the log-rank test. Prognostic factors were identified using univariate and multivariate Cox hazard analyses. Subgroup analyses were conducted to assess the effects of MLRT on specific patient populations. We analyzed data from 1157 patients with mNPC. Patients who received MLRT had significantly better OS than those who did not, both in the original (28 vs. 21 months) and PSM cohorts (26 vs. 23 months). MLRT was identified as an independent favorable predictor of OS in multivariate analyses, with hazard ratios of 0.67. The subgroup analysis results indicated that radiotherapy effectively treated liver, lung, and bone metastatic lesions, particularly in patients with a limited tumor burden. Higher total radiation doses of MLRT (biologically effective dose (BED) ≥ 56 Gy) were associated with improved OS, while neither radiation technique nor dose fractionation independently influenced prognosis. MLRT offers survival advantages to patients diagnosed with mNPC. Patients with limited metastatic burden derive the most benefit from MLRT, and the recommended regimen for MLRT is a minimum BED of 56 Gy for optimal outcomes. [ABSTRACT FROM AUTHOR]

• Induction chemotherapy significantly improved survival outcomes in unselected patients with LN-positive stage III NPC. • Induction chemotherapy worked better for patients with N2 disease, grade 2–3 ENE, and LDH > 170U/L. • Patients with grade 0–1 ENE combined with LDH ≤ 170U/L could be spared from futile IC. • CNN may not be a good risk factor for tailoring a personalized treatment plan. To investigate the role of induction chemotherapy (IC) in lymph node-positive (LN-positive) stage III nasopharyngeal carcinoma (NPC) receiving concurrent chemoradiotherapy (CCRT). In total, 627 patients with newly diagnosed LN-positive stage III NPC receiving CCRT or IC plus CCRT were included. The primary endpoint was progression-free survival (PFS). Propensity-score matching (PSM) was conducted to balance the intergroup covariates. Kaplan-Meier method with log-rank test was employed to compare survival curves. Subgroup analyses were conducted based on baseline characteristics. After 1:1 PSM, 414 patients were identified (207 patients per group). Compared with CCRT, IC plus CCRT provided better survival (5-year PFS 88.4% vs. 78.6%, P = 0.01; overall survival [OS] 94.8% vs. 85.3%, P = 0.003; and distant metastasis-free survival [DMFS] 93.1% vs. 85.6%, P = 0.03). The IC beneficial effects on PFS were mainly present in patients with grade 2–3 ENE, elevated serum lactate dehydrogenase (LDH > 170U/L), and N2 disease. Patients with grade 2 CNN had comparable PFS benefits to those with grade 0–1 CNN. For patients with grade 0–1 ENE combined with LDH ≤ 170U/L, survival between the two groups was similar with 5-year PFS 93.6% vs. 90.4% (P = 0.50), OS 94.2% vs. 93.0% (P = 0.72), and DMFS 98.6% vs. 97.7% (P = 0.98). Adding IC before CCRT improved survival in LN-positive stage III NPC patients. Additional IC did not provide better survival for patients with grade 0–1 ENE combined with LDH ≤ 170U/L and could be avoided in this population. CNN may not be a good risk factor for tailoring a personalized treatment plan. [ABSTRACT FROM AUTHOR]

Purpose: Chemotherapy use remains controversial for stage II nasopharyngeal carcinoma (NPC). This retrospective study was conducted to identify whether chemoradiotherapy was associated with better survival compared to radiotherapy.Materials and Methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried for stage II NPC patients between 2004 and 2015. Patients were divided into radiotherapy and chemoradiotherapy groups. Overall survival (OS) and cancer-specific survival (CSS) were examined using the Kaplan-Meier method, Cox proportional hazards models, and propensity score matching analyses.Results: This study examined 908 patients, including 102 receiving radiotherapy and 806 receiving chemoradiotherapy. Chemoradiotherapy was associated with 5-year OS (78.01% vs. 75.12%; p = 0.22) and CSS (78.92% vs. 78.26%; p = 0.40) rates comparable to those of radiotherapy. Propensity score matching analyses demonstrated similar OS (HR: 0.63, 95% CI: 0.36--1.10; p = 0.10) and CSS (HR: 0.77, 95% CI: 0.41-1.48; p = 0.44) rates with radiotherapy. Age >60 years and non-Asian patients were associated with worse survival.Conclusion: This study revealed that chemoradiotherapy showed similar survivals to stage II NPC patients compared with radiotherapy. Due to the limitations of SEER database, further studies should be performed to verify the results. [ABSTRACT FROM AUTHOR]